Australian researchers have reported that drug resistance is likely to worsen in only a quarter of patients during the interval between blood being drawn for a resistance test and delivery of the result.
The risk appears to be greatest in patients with extensive prior treatment experience – especially in relation to acquiring new reverse transcriptase mutations.
The results, reported in the January edition of the Journal of Acquired Immune Deficiency Syndromes, come from a sub-study of the CREST study, a randomised comparison of genotyping and Virtual Phenotype. Patients were eligible to join the CREST study if they had viral load above 1,000 copies/ml and were prepared to change therapy on the basis of a resistance test result.
The sub-study recruited 30 patients, 18 receiving protease inhibitor based therapy, eight receiving NNRTI-based therapy, two receiving triple nucleoside regimens and two receiving regimens containing drugs from all three classes.
The sub-study evaluated the changes in resistance profiles during the period between two blood samples, taken a median of 37 days apart.
Thirty per cent of patients (n= 9) experienced changes in NRTI resistance during this period. In two cases some mutations emerged whilst others disappeared, but two patients lost mutations without gaining any new ones. There was no clear pattern to the disappearance of mutations, but those who gained resistance mutations (n=5) had greater treatment experience (8.7 years vs 5 years, p=0.02). The majority of those who gained resistance mutations accumulated thymidine analogue-associated mutations that might compromise future response to abacavir, zidovudine (AZT) and stavudine (d4T).
The authors say that mutations probably disappeared because they were associated with prior therapies rather than the current regimen. For example, a patient who lost the M184V mutation during rebound was receiving a combination of ddI, d4T and nelfinavir, none of which would maintain selective pressure on the M184V mutation.
Only one protease change was observed, in a patient receiving nelfinavir. This individual acquired the M46I mutation, having already developed the L90M mutation.
The authors conclude “it is more unlikely than likely that significant mutations will be generated if the time for testing and review is kept to within approximately 5 weeks.”
Birch C et al. Limited evolution of HIV antiretroviral drug resistance-associated mutations during the performance of drug resistance testing. JAIDS 32: 57-61, 2003.